Efficient Synthesis of Diaryl Quaternary Centers by Rh(II)/Xantphos Catalyzed Relay C−H Functionalization and Allylic Alkylation

Abstract

A three‐component reaction of N, N‐disubstituted aniline, α‐diazo ester, and an allylic electrophile has been realized by [Rh(II)]2/Xantphos catalysis, providing a direct access to various aniline derivatives bearing diaryl allylic quaternary centers in good yields. The synthetic utility of this protocol was demonstrated by facile derivatization of the products for preparation of biologically relevant molecules and structural scaffolds, which offers a high potential for increasing the molecular diversity. Mechanistic studies identified α, α‐diarylacetate species as an active intermediate, thereby revealing the presence of a C(sp2)−H functionalization of aniline derivatives/allylic alkylation cascade in this attractive catalytic transformation.

Selective Construction of All-Carbon Quaternary Centers via Relay Catalysis of Indole C–H Functionalization/Allylic Alkylation

“…Based on previous reports − and the experimental results, herein, a putative process for this reaction is shown in Scheme . First, phosphine-free or Xantphos coordinated [Rh­(II) 2 ] can efficiently catalyze the carbene insertion process to give the intermediate 4 (Cycle I).…”

“…In continuation of our effort in exploring new MCRs through dirhodium­(II) catalysis, − herein, we report a dirhodium­(II)/Xantphos catalyzed three-component reaction of readily accessible indoles, diazo compounds, and allylic electrophiles, leading to the formation of C3-substituted indoles with an allyl-bearing all-carbon quaternary center in a single operation. Various side reactions, such as cyclopropanation between the diazo compounds and CC bond, as well as the competitive direct C2- or C3-allylic alkylation of indoles were avoided.…”

Cooperative Bimetallic Catalysis via One‐Metal/Two‐Ligands: Mechanistic Insights of Polyfluoroarylation‐Allylation of Diazo Compounds

“…The study was commenced by a preliminary survey of our previous dirhodium(II)/Xantphos system in the reaction of pentafluorobenzene 1 a , α‐diazo ester 2 a , and allylic substrate 3 a [15–18] . Unfortunately, the system failed to furnish the target product 4 a (Table 1, Entry 1).…”

“…The study was commenced by a preliminary survey of our previous dirhodium(II)/Xantphos system in the reaction of pentafluorobenzene 1 a, α-diazo ester 2 a, and allylic substrate 3 a. [15][16][17][18] Unfortunately, the system failed to furnish the target product 4 a (Table 1, Entry 1). Because in the presence of a base, some Cu I or Ag I complexes can activate pentafluorobenzene via formation of the corresponding pentafluorophenyl metal species, [24,26,27,29] we tried to introduce a copper(I) or silver(I) salt with a 1,10-phenanthroline ligand as a co-catalyst into the system.…”

“…Despite these remarkable advances, however, the difunctionalization of diazo compounds via synergistic bimetallic catalysis has been much less explored in MCRs so far [12–14] . Recently, our group developed a dirhodium(II)/Xantphos system for the catalysis of three‐component reactions, typically involving a nucleophile, a diazo compound, and an allylic electrophile via a relay carbene insertion‐allylic alkylation process (Scheme 1b) [15–18] . However, the types of nucleophiles are still limited in these systems, and highly electron‐rich nucleophiles (e.g., amine NH, N , N ‐disubstituted aniline, phenol, and indole) are often a prerequisite for smooth reactions, which limits the diversity of the obtained products.…”